Study of EHS type IV collagen lacking Goodpasture's epitope in glomerulonephritis in rats.
Study of EHS type IV collagen lacking Goodpasture's epitope in glomerulonephritis in rats.
复制标题
缺乏 Goodpasture 表位的 EHS IV 型胶原蛋白在大鼠肾小球肾炎中的研究。
DOI：
10.1038/ki.1995.53
复制
发表时间：
1995
影响因子：
19.6
通讯作者：
Sturgill,BC
中科院分区：
文献类型：
--
作者：
Bolton,WK;Luo,AM;Fox,PL;May,WJ;Sturgill,BC
Study of EHS type IV collagen lacking Goodpasture's epitope in glomerulonephritis in rats. The Goodpasture's epitope has been mapped to the α3non-collagenous chain (NC1) of type (IV) collagen [α3col(IV)]. We have developed a model of experimental autoimmune glomerulonephritis (EAG) in rats immunized once with collagenase solubilized GBM (csGBM). Engelbreth-Holm-Swarm (EHS) tumor contains abundant col(IV) with little or no α3col(IV). To test the hypothesis that antigens related to Goodpasture epitope are required to produce EAG in our model, we immunized rats once with 40 µg csEHS. Positive controls immunized with csGBM developed typical EAG with GBM bound antibody, proteinuria, and glomerulonephritis. EHS rats developed circulating and bound antibody to mesangium and tubular basement membrane with minimal GBM deposits, but did not develop proteinuria or glomerulonephritis. Although circulating antibody in EHS rats bound to csGBM by ELISA, there was no binding in ELISA to M2 antigen containing the Goodpasture epitope while EAG rat's serum did bind. By Western blot with antisera to Goodpasture epitope, EHS antigen was less complex than GBM in the monomer/dimer regions and appeared to lack NC1 corresponding to α3col(IV). Blotting with sera from EHS rats demonstrated reactivity to various components of GBM but not to α3col(IV). EAG sera and renal eluates bound to α3col(IV). EAG rats evidenced cell mediated immunity while EHS rats did not (stimulation index EHS 1.1, EAG rats 8.0). These studies show that the development of antibody to col(IV) in a setting conducive to EAG does not cause EAG in the absence of α3col(IV) NC1, that the antibody response in EHS rats was not associated with a cellular response to the antigen and that an epitope on the same NC1 α3col(IV) which contains the Goodpasture epitope appears necessary to induce EAG in this model. These studies further implicate the α3col(IV) as a pathogenetic factor in the development of Goodpasture syndrome in humans as well as a marker of disease.
